Kondo E, Matsui H, Matsuo Y, Shibasaki F
Second Department of Pathology, University Medical School.
Nihon Rinsho. 1998 Nov;56(11):2973-81.
Calcineurin, serine/threonine phosphatase2B, is well known as a target of immunophilin-immunosuppressant complex such as cyclophilin-cyclosporinA and FKBP -FK506. It has been disclosed that Calcineurin is involved in interleukin 2 gene activation pathway lead to T lymphocyte proliferation, however, its functions as a multipotential factor still remains unknown. Here we mention about a new aspect of Calcineurin-involved pathway through its direct interaction to Bcl-2, an apoptosis suppressor. This direct binding of Calcineurin to Bcl-2 results in blockage of KFAT4 nuclear import by the prevention of Calcineurin-targetted dephosphorylation of NFAT4. Moreover, the tight binding between Calcineurin and Bcl-2 facilitate Bcl-2 activation as a apoptosis inhibitor through dephosphorylation of phosphorylated form of Bcl-2 serving to apoptosis regulation.
钙调神经磷酸酶,即丝氨酸/苏氨酸磷酸酶2B,作为亲免素 - 免疫抑制剂复合物(如亲环蛋白 - 环孢素A和FK506结合蛋白 - FK506)的作用靶点而广为人知。据披露,钙调神经磷酸酶参与白细胞介素2基因激活途径,从而导致T淋巴细胞增殖,然而,其作为一种多潜能因子的功能仍然未知。在此,我们阐述了钙调神经磷酸酶相关途径的一个新方面,即它与凋亡抑制因子Bcl-2的直接相互作用。钙调神经磷酸酶与Bcl-2的这种直接结合,通过阻止钙调神经磷酸酶靶向的NFAT4去磷酸化,导致NFAT4核输入受阻。此外,钙调神经磷酸酶与Bcl-2之间的紧密结合,通过使参与凋亡调节的磷酸化形式的Bcl-2去磷酸化,促进Bcl-2作为凋亡抑制剂的激活。